J. Org. Chem. 1980,4fj, 3613-3618 3613

sterically induced flattening in hydrocarbons.21p22 The data reported here indicated that hybridization at

nitrogen is an important factor in determining 6N, a hy- pothesis which 0ugh.t to be tested on other amino com- pounds. Because the amount of pyrimidality a t nitrogen is quite difficult to measure experimentally (a complete structure determination is now required), better under- standing of the various factors influencing aN could ulti- mately promote a spectroscopic way of estimating the hybridization at nitrogen, which we expect to be important in determining the reactivity of amino compounds.

Experimental Section Natural-abundance I5N Fourier transform NMR spectra were

obtained on a Varian XL-100-15 spectrometer equipped with a V4412 (12 mm) probe and a Varian FT data system using the Gyroobserve option. Spectra were recorded at a spectral width of 5120 Hz, and 4096 data points (1.25 Hz/point) were obtained. A pulse width corresponding to a 30” flip angle was used at a 1.6-2.0-8 repetition rate. Sample concentration was typically 1.5-3.0 M in 1/1 (v/v) acetone-d6/nitromethane. This solvent mixture provided bothL the internal deuterium lock and nitro- methane reference.% The solutions were approximately 0.085 M in C r ( a ~ a c ) ~ to shorten relaxation times. Sample volumes of 2-3 mL were employed. Adequate signal-to-noise ratios were observed for 3 M hydrazine samples having two equivalent ni- trogens in 4 h; more dilute samples required up to 16 h of data acquisition.

The observed 16N chemical shifts are internally consistent to f0.2 ppm relative to CH3NO2 While we recognize the deficiencies of internal standards for accurate and reproducible absolute chemical shift determination,% we feel that for compounds of

(25) Internal referencing has been suggested to be the method of choice in the presence of paramagnetic relaxation reagents: DiGioia, A.; Lichtar, R. L. J. Magn. Reson. 1977,27,431; Sibi, M. P.; Lichter, R. L. J. Org. Chem. 1977, 42, 2999.

(26) Witanowski, M.; Stafaniak, L.; Szymafiski, S.; Januszewski, H. J. Magn. Reson. 1977, 28, 217. (b) Srinivasan, P. R.; Lichter, R. L. Ibid. 1977,28, 227.

similar structural type run under similar conditions these con- ditions provide the most consistent and convenient means of obtaining relative shifts. A study of chemical shift changes with substrate concentration was undertaken for 1,2-dimethyl-1,2- diethylhydrazine, in which a 0.2-ppm d o d e l d shift was observed when the hydrazine concentration was increased from 1.3 to 2.7 M at a constant Cr(aca& concentration of 0.087 M. Almost all of our hydrazine samples fall in this concentration range. The effect of paramagnetic relaxation reagents on 16N shifts has been noted.% The circumvention of such effects by using internal referencing has been found to be quite adequate. Varying the concentration of Cr(aca& from 0.05 to 0.10 M resulted in less than a 0.1-ppm change in the chemical shift for both nitrogens of isobutyltrimethylhydrazine relative to internal nitromethane, but a 0.66-ppm upfield shift relative to external D16N03 [the hydrazine chemical shift was 294.18 ppm upfield from external Dl5NO3, 1.0 M in DzO, which is 4.33 ppm upfield from neat external nitromethane, and the hydrazine shift was 295.70 ppm upfield from internal nitromethane, all experiments quoted being at 0.10 M Cr(acac)J.

NMR spectra were obtained at 15.9 MHz on a JEOL FX-60 spectrometer.

The tetraakylhydrazines were prepared by previously reported methods?$ Purification and drying was performed by distillation and/or allowing the sample to stand over NaOH pellets. Solids were crystallized or sublimed, as appropriate.

Acknowledgment. We thank the donors of the Pe- troleum Research Fund, administered by the American Chemical Society, and the National Science Foundation for partial financial support of this work and Dr. D. F. Hillenbrand for valuable assistance in obtaining the 16N spectra.

Registry No. 1, 6415-12-9; 2, 50599-41-2; 3, 23337-93-1; 4, 21849-74-1; 5,60678-65-1; 6,52598-10-4; 7,68970-04-7; 8,426740-9; 9, 60678-69-5; 10, 60678-71-9; 11, 6130-94-5; 12, 6523-29-1; 13, 26163-37-1; 14, 3661-15-2; 15, 5721-43-7; 16, 14287-92-4; 17, 14287- 89-9; 18, 18389-95-2; 19,38704-89-1; 20,74096-71-2; 21,5397-67-1; 22, 23211-28-1; 23,60387-16-8; 24, 63892-83-1.

Molecular Asymmetry in trans-Thiacycloalkenes. 2. Barriers to Interconversion of Diastereomeric Conformers of 2-Substituted Nine- to

Eleven-Membered (E)-Thiacycloalk-4-enes’

Vanda Cer6, Claudio Paolucci, Salvatore Pollicino, Edda Sandri, Antonino Fava,* and Lodovico Lunazzi*

lstiituto di Chimica Organica, Universitd di Bologna, Viale Risorgimento 4, 40136 Bologna, Italy

Received February 25, 1980

trans-Thiacycloalk-4-enes of ring size 9 to 11 carrying a substituent (CH3 or COOCHJ at Cz were synthetized. These species have two elements of chirality (a plane and a center) and exist as diastereomeric pairs which may interconvert via a conformational process (180” revolution of the ?r plane inside out the ring). The energy barrier for this process has been measured by dynamic NMR and found to be 16.4,10.7, and 8.3 (or 7.0) kcal/mol for the 9-, lo-, and 11-membered-ring compound, respectively, lower than those for their carbocyclic analogues. The lower barriers may arise from the heteroatom across the ring, which, unlike the corresponding carbon in the homocyclic counterpart, carries no ligand and allows for less steric compression in the transition state.

Eight-membered and larger rings may accommodate a double bond of E configuration. Rings having this feature are chiral enantiomeric pairs2 whose interconversion occurs through configurational inversion of a chiral plane. This

(1) Paper 1 in this series: Cere, V.; Pollicino, S.; Sandri, E.; Fava A. J. Am. Chem. SOC. 1978,100, 1516.

(2) (a) Blomquist, A. T.; Lin, L. H.; Bohrer, J. C. J . Am. Chem. SOC. 1962, 74, 3643. (b) Prelog, V. In “Perspectives in Organic Chemistry”; Todd, A,, Ed.; Interscience: New York, 1956 p 129. (c) Cope, A. C.; Ganellin, C. R.; Johnson, H. W., Jr.; Van Auken, T. V.; Winkler, H. J. S. J. Am. Chem. SOC. 1963,85, 3276.

process requires a 180’ rotation of the sp2 plane around the u bonds adjacent to the ?r bond and involves the passage of one of the olefinic hydrogens inside out the ring via a transition state in which the olefinic H was moved against the atoms across the ring and the ligands thereon.

(3 0022-3263/80/1945-3613$01.00/0 0 1980 American Chemical Society

3614 J. Org. Chem., Vol. 45, No. 18, 1980

The height of the energy barrier for this process depends on ring size. Thus for carbocycles the barrier decreases from 35 kcal mol-' for (E)-cyclooctene3 to 19 and 11.7 kcal mol-' for (E)-cyclononene4 and (E)-cy~lodecene.~

The nature of the atoms across the ring also affects the barrier. Thus in going from (E)-cyclooctene to (E)-thia- cyclooct-4-ene, in which the methylene at position 5 has been replaced by an S atom, the barrier drops by 5 kcal mol-'.' The lower barrier is likely to arise from the het- eroatom across the ring, which, unlike the corresponding carbon in the homocyclic counterpart, carries no ligands, allowing for less steric crowding in the transition state. When ring size is increased, the differential barrier for chiral inversion, homocyclic vs. heterocyclic, is expected to gradually diminish.

As part of a broader study of the chemical and structural properties of medium-size heterocyclic olefins>6'@ we have synthesiied (E)-thiacycloalk-4-enes of ring size 9-11, having a substituent (CH3 or COOCH3) at C2 (1-3). Be-

Cer6 et al.

R

l a , n = 1; R = CH, lb, n = 1; R = CO,CH, 2, n = 2; R = CH, 3, n = 3; R = CO,CH,

side the chiral plane, these species possess a second ele- ment of chirality, a chiral center a t C2, and therefore are diastereomerically rather than enantiomerically related. They give rise, a t low temperature, to separate sets of resonances in the 13C NMR spectrum, and their inter- conversion may be studied by dynamic '% NMR methods. The present paper reports this study.

Results and Discussion Synthesis. The required 2-substituted (E)-thiacyclo-

alk-4-enes were obtained via three-carbon ring expansion by [2,3] sigmatropic rearrangement of cyclic sulfonium ylides,' which for ring size six and larger produces cyclic homoallylic sulfides largely of E configuration ( E / Z 1 20).79s Our initial plan was to synthetize 2-methyl sub- stituted thiacycloalk-4-enes by rearrangement of 1- ethylides obtained by in situ deprotonation of 1-ethyl sulfonium salts. The method works well with the six- membered (n = 1) sulfonium salt, from which only prod- ucts of ring expansion are obtained. It works less well with the seven-membered salt which, along with ring expansion, gives elimination products. I t fails completely with the eight-membered salt (see Scheme I).

As the cyclic sulfonium salt grows in size and ring strain, &elimination reactions that bring about ring opening be-

(3) Cope, A. C.; Pawson, B. A. J. Am. Chem. SOC. 1965, 87, 3649. (4) Cope, A. C.; Banholzer, K.; Keller, H.; Pawson, B. A.; Whang, J.

J.; Winkler, H. J. S. J . Am. Chem. SOC. 1965,87, 3644. (5) (a) Binsch, G.; Roberta, J. D. J. Am. Chem. Soc. 1965,87,5157. (b)

Noe, E. A.; Wheland, R. C.; Glazer, E. S.; Roberta, J. D. Ibid. 1972, 94, 3488.

(6) (a) Cere V.; Guenzi, A.; Pollicino, S.; Sandri, E.; Fava, A. J. Org. Chem. 1980,45, 261. (b) Calderoni, C.; Cer6, V.; Pollicino, S.; Sandri E.; Fava, A,; Guerra, M. J. Org. Chem., in press.

(7) (a) Vedejs, E.; Hagen, J. P. J. Am. Chem. SOC. 1975,97,6878. (b) Vedejs, E.; Hagen, J. P.; Roach, B. L.; Spear, K. J. Org. Chem., 1978,43, 1185. (c) Cer6, V.; Paolucci, C.; Pollicino, S.; Sandri, E.; Fava, A. Ibid. 1978, 43, 4826. (d) Vedejs, E.; Arco, M. J.; Powell, D. W.; Renga, J. M.; Singer, S. P. Ibid. 1978, 43, 4831.

(8) CerC, V.; Paolucci, C.; Pollicino, S.; Sandri, E.; Fava, A. J. Org. Chem. 1979,44, 4128.

Scheme I

6%

90 % 4c, n = 3

8 8 4 % +

come more important and take over completely at ring size eight.

Since no opening had been previously observed in the ring expansion of l-methyl-2-~inylthiepanium,~~ the be- havior of the l-ethyl salt appears likely to be related to the lesser acidity of the exocyclic a protons. Their removal by base is not competitive with base catalyzed /3-elimina- tion in those ring systems where elimination results in the fission of a relatively strained ring. This observation and other 0nes,7~*~ according to which ring expansion occurs without problems from eight- and nine-membered sulfo- nium salta carring an activated exocyclic C-H (e.g., S-allyl9 and S -~a rbe thoxy~~ derivatives), indicate that the desired 2-substituted eleven-membered thiacycloalk-4-ene could be obtained from a stabilized ylide. A carbomethoxy stabilized ylide, prepared in situ by thermal Cu(I1)-cata- lyzed decomposition of methyl diazoacetate'O in the presence of 2-vinylthiocane, gives the expected eleven- membered 2-carbomethoxy derivative as the major prod- uct.

3

Since the change from methyl to carbomethoxy may affect the energy barrier for chiral inversion, the carbo- methoxy derivative lb of the nine-membered ring was also prepared. Its dynamic 13C NMR behavior was observed along with that of la.

Dynamic '3c NMR. Table I lists the 13C NMR shifts for the conformational isomers of compounds la, lb, 2, and (partially) 3. The data for the corresponding eight-mem- bered-ring compounds are also reported.'^^^ For compar- ison, the shifts of the corresponding unsubstituted cyclic olefins are also included.

The room-temperature 13C NMR spectrum of la in CDC13 displays two sets of signals. The line width of the weaker signals appears to be larger than that of the more intense companions. This indicates a slow exchange be- tween two unequally populated sites." Indeed, on low-

(9) (a) Vedejs, E.; Mullins, M. J.; Renga, J. M.; Singer, S. P. Tetra- hedron Lett. 1978, 519. (b) Schmid, R.; Schmid, H. Helu. Chim. Acta 1977,60, 1361.

(IO) Ando, W.; Kondo, S.; Nakayama, K.; Ichibori, K.; Kohoda, H.; Yamato, H.; Imai, I.; Nakaido, S.; Migita, T. J. Am. Chem. SOC. 1972,94, 3870. Ando, W.; Yamada, M.; Matzusaki, E.; Migita, T. J. Org. Chem. 1972, 37, 3791.

J. Org. Chem., Vol. 45, No. 18, 1980 3615

Table I. ring size R isomer C, c4 c, c, c, c, c, c, CI, c,, other

3C NMR Shifts (ppm from Me,Si) of (E)-Thiacycloalk-4-enes and their Diastereomeric 2-Substituted Derivativesu

-- 8 Hb*c 137.5 130.4 43.5 37.8 (36.8) (35.2) (34.8)

44.9 (35.7) (34.8) (33.8) 21.2m 41.8 (37.7) (35.01 25.9 21.4m

CH,b,d RR,SS CH,b*d RS,SR

CH,b$e major CHSbpe minor COOCH,f major COOCH3f minor

CH,g majac CH,g minor

COOCH,

9 Hbic

10 Hbvc

11 Hb9h

136.6 131.7 139.6 127.5 134.6 126.6 134.8 127.4 133.9 128.1 136.3 124.7 135.6 125.6

[ 131.61 [ 130.31 [ 131.41 [ 130.51 [ 132.01 [ 130.21 [ 134.11 [ 128.51 [137.7Ik [127.1]

Shifts in parentheses or in

Reference 20. for the same carbon atom. Cl,, -90 a C. text and footnotes k and 1.

54.3 49.9

(37.6) 46.5 48.5 51.6 51.3

(34.2) 45.8 42.8

50.4 (35.7)

36.2) (33.2j (32.6j (26.0) (25.6) 42.5 (36.5) (32.2) (25.1) (25.0) 23.3m 38.9 (36.2) (33.8) (30.0) (29.0) 21.4 37.8 (35.8) (33.0) (25.4) (24.4) 172.0," 51.7O 35.4 (34.6) (33.0) (28.1) (27.5) 51.3O 34.2) (33.5) (31.3) (27.2) (25.4) (23.6) 44.7 (32.8) (30.0) (27.7) (25.6) (23.9) 22.4m 37.7 (32.7) (34.1) (27.1) (25.2) (23.9) 23.gm 33.8) (33.7) (33.0) (27.7) (26.8) (26.3) (25.1) 36.6 (34.7) (30.4) (28.9) (27.2) (26.8) (25.1) 176.6," 52.9O

brackets are interchangeable ; for diastereomeric pairs, however, shifts in the same column are CDCl, solvent. Reference 7c. Reference 1. e At 0 C. f C,Cl, solvent, at 0 C. g CD,-

! At -120 'C, 138.2 and 137.3. FAt -120 'C, 49.6 and 49.1. CHF,Cl solvent, -20 C; avera ed shifts of two about equally populated conformers. See

CH,. CO. OCH,.

Table 11. Activation Parameters for Interconversion of Diastereomeric Conformers of 2-Substituted (E)-Thiacycloalk-4-enes

compd solvent temperature range, K AG+, kcal/mol AH', kcal/mol AS', kcal/mol

l a CDCl, 312-333 16.3, c 0.4O! 15.9 t 0.6 - 1 . 5 t 2 l b c2c14 326-332 17.1, c 0.15O!

3 CHF,Cl 161-168 8.3 c 0.2 148-153 7.0 f 0.3

2 CD,Cl, 212-243 10.7, f O.Ogb 10.1 t 0.6 -3 k 3

(I For racemization of optically active (E)-cyclononene, AG+ = 19.1 f 0.2 kcal/mol., For (E)-cyclodecene-1,2,4,4,9,9- d, and 3,3-difluoro-tra~ns-cyclodecene, AG+ = 1 1.85a and 12.2 kcaUm01.5~

ering the temperature to 0 "C, the two sets of lines sharpen to the same line width (intensity 70:30; see Table I for shifts). The 13C signah of la broaden and coalesce to yield a sharp nine-line spectrum on warming above room tem- perature (about 75 "C, see Experimental Section). The kinetic parameters of the exchange process were evaluated by computer simulation of the line shapes.12 Although any pair of corresponding signals may be used, the purpose is better served by pairs of lines having the largest chem- ical-shift difference (unencumbered by overlapping sig- nals). The two pairs of low-field saturated-carbon lines C2 (48.5 and 46.5 ppm) and C3 (42.5 and 38.9 ppm), re- spectively, were suitable. The second pair, with a greater shift difference, allowed the line shape to be followed in a wider temperature range (312 to 335 K against 312 to 321 K). The values of the rate constants obtained at each temperature from either pair of lines were averaged and least-squares fitted t o the Eyring equation to give the kinetic parameters reported in Table 11. Table I1 also lists the corresponding parameters for the other ring systems. Since, for both la and 2, AS* was found to be zero within experimental errors (Table 11), AG* is considered to be essentially temperature independent and will be used as the measure of the interconversion barrier.

The room-temperature spectrum (CD2C12 solvent) of the ten-membered-ring compound 2 shows ten signals (see Experimental Section) which on cooling at -90 "C separate into two sets (intensity 70:30; Table I). The two pairs of low-field saturated-carbon signals were used to analyze line shape. In this case the two pairs could not be analyzed independently of each other, because one pair crosses over

(11) Binsch, G. In "Dynamic NMR Spectroscopy"; Jackman, L. M., Cotton, F. A., Eds.; Academic Press Inc.: New York, 1975; Chapter 3.

(12) Binsch, G.; Klein, D. A. Q.C.P.E. DNMR Program No. 140, University of Indiana, Bloomington, IN.

(13) Dale, J. Top. Stereaochem. 1976, 9, 199. See, in particular, the discussion on pp 253-255.

k(s - ' )

Figure 1. Experimental (left) and computer-simulated (right) line shapes of Cz and C3 of compound 2 as a function of tem- perature ("C).

the other: the 45.8-ppm line was found to exchange with the line at 42.8 ppm, and the 44.7-ppm line with the line at 37.7 ppm (see Figure 1). When the temperature was lowered further (below -110 "C, CHF2C1 solvent), a second dynamic process became evident; however, no region of the '3c spectrum was amenable to accurate line-shape analysis. Nonetheless, since the chemical-shift differences of the lines generated by the second process are in the range 10-50 Hz and broadening occurs between -110 and -125 "C, the barrier for this second process can be estimated to be in the 7-8 kcal/mol range. The higher of the two

3616 J. Org. Chem., Vol. 45, No. 18, 1980

barriers would be unreasonably elevated for a simple conformational change in a ten-membered ring and, in analogy with (E)-cy~lodecene,~J~ can be assigned to the process of rotation of the trans double bond through the ring.

In CHF2Cl at -20 "C, the eleven-membered compound 3 displays a sharp 12-signal spectrum (Table I). Stepwise lowering of the temperature down to -140 "C disclosed two dynamic processes. The more highly activated process was followed in the range -105 to -112 "C by monitoring the low-field aliphatic resonance at 50.4 ppm and the high-field olefinic resonance at 127.1 ppm. Both split into two equally intense signals a t low temperature. The second process was evinced by a further splitting of the signals a t lower temperature. The 13C spectrum is extremely complex and only one carbon resonance (the olefinic car- bon a t 137.7 ppm) was found to be adequate for line-shape analysis. The two barriers are too close to one another to decide which of the two corresponds to the inversion of the chiral plane. However, their very closeness makes the assignment of little importance.

The conformational barriers reported in Table I1 con- firm the expectations that for these heterocyclic E olefins the inversion of the chiral plane (involving a 180" rotation of the double bond through the ring) is less activated than for the carbocyclic homologues. The differential barriers, carbocyclic vs. heterocyclic, diminish with increasing ring size (Table 11).

Unlike the eight-membered-olefin case,' where it was possible to attempt a rationalization (later confirmed to be correct)6b of the I3C NMR shifts in terms of confor- mation and configuration of the diastereomers, in the present cases the 13C shifts offer no clue to the prevailing conformation(s). Under these circumstances no analysis can be attempted for the interconversion processes. Consider the nine-membered olefin and its 2-methyl de- rivative la. If the hypothesis is given that the ring con- formation is similar to the C2 conformation of (E)-cyclo- nonene,14 then the two diastereoisomers of la would differ for the orientation of the Me group, as depicted. Ac-

H H

Cer6 et al.

2R.4S 2S.4S

cording to the argument developed for assigning the con- figuration of the eight-membered-ring homologues,' the RS,SR isomer is expected to have both C4 and Cg upfield (y-effect) with respect to the SS,RR isomer, whose C4 and C9 shifts would in turn be about the same as those in the unsubstituted ring compound. The data in Table I do not bring forth this prediction: for both diastereomers of la the shifts of C4 are very close to each other, very close in turn to that of the unsubstituted oelfin. Neither dia- stereomer displays the y-effect on C4 that would be ex- pected if both isomers adopt the twist conformation as- sumed. An explanation is that the RS,SR isomer adopts a different ring conformation, which allow a more effective relief of the strain that would arise from the Me group in a gauche arrangement to both C4 and Cg. Such a re- quirement might be satisfied by a crown conformation, below, in which the dihedral angles C4C3C2CH3 and CgS- C2CH3 would be about 150°, and for which no appreciable y-effect would arise.

The idea that the two diastereomers adopt different ring conformations is supported by other shift considerations. (14) Ermer, 0.; Lifson, S. J. Am. Chem. SOC. 1973, 95, 4121.

Although a precise assignment of C9 could not be made, Table I shows a close correspondence between the shifts of the unsubstituted ring compound and those of the minor conformer of la (except C2 and C3, of course). On the other hand, the major conformer has the two uppermost carbon shifts a t very low field (30.0 and 29.0 ppm), indicating downfield shifts of at least 4.9 and 4.0 ppm. A deshielding of this magnitude, while unprecedented for carbons three or more bonds away from the CH3 substituent, could be justified by a different ring shape. We suggest that the major conformer of la adopts a ring conformation different from that of either the minor conformer or the unsubsti- tuted ring.

A similar analysis of the ten-membered homologues leads to conclusions analogous to those for the nine-mem- bered olefins. I t is evident that more detailed work is necessary (high-field 'H, 2H, and NMR, molecular- mechanics calculations) to gain a satisfactory under- standing of the static and dynamic properties of these molecules. Work in this direction has begun.

Experimental Section General. Proton NMR spectra were recorded at 60 MHz on

a JEOL C-60 HL instrument and at 100 MHz on a Varian %lo0 operating in the CW mode. Proton noise-decoupled 13C NMR spectra were recorded at 25.16 MHz with a Varian XL-100 by Fourier transform. Unless otherwise stated, 'H and '% shifts are given in parts per million from Me& in CDC13 solvent. For low-temperature experiments in CHF2Cl solvent, the samples were prepared by connecting the 10-mm NMR tube, containing the compound and some acetone-d8 for deuterium locking, to a vacuum line. Gaseous CHF2Cl was then admitted and condensed with liquid N2, the tube being sealed in vacuo. The sample was allowed to warm to just below room temperature before insertion into the precooled spectrometer. The temperature was measured with a thermocouple inserted in a dummy tube before or after each spectral determination. Spectral simulations were run, using the DNMR program developed by Binsch,12 on the computer facility of the University of Bologna.

GLC analysis was carried out with a Hewlett-Packard 5700 instrument equipped with a he-ionization detedor; preparative GLC separations were performed with a Varian-Aerograph 712 instrument. Two types of stationary phases were used, (A) 10% XE 60 and (B) 7% C 20M, both on Chromosorb W, 60-80 mesh.

Solvents and reagents were obtained dry as follows: methylene chloride, tert-butyl alcohol, benzene, and diisopropylamine were distilled from calcium hydride. Tetrahydrofuran, dried over sodium and distilled, was redistilled immediately before use.

2-Vinylthiane and 2-vinylthiepane were prepared by base-catalyzed dehydrobromination of 2-(2-bromoethyl)thiane and -thiepane, respectively, as described previo~s ly .~~

2-Vinylthiocane. Attempts to prepare the title comp'ound from 2-(2-bromoethyl)thiocane by the dehydrobromination me- t h ~ d ~ ~ failed, owing to extensive isomerization of the initially formed terminal olefin to internal olefins under the conditions required for dehydrobromination. The synthesis was eventually achieved by coupling 2-chlorothiocane with vinylmagnesium bromide by the procedure previously described for 2-vir1ylthiane.7~ A benzene solution of 2-chlorothiocane, freshly prepared by the procedure of Tuleen and BennetP from thiocane (5.6 g, 43 mmol, in 95 mL) and N-chlorosuccinimide (5.78 g, 43 mmol), was added dropwise over 45 min to an ice-cooled solution of the Grignard reagent [prepared from 9 mL (128 mmol) of vinyl bromide and 3 g (123 "01) of magnesium in 160 mL of THF]. After warming to room temperature, the reaction mixture was decomposed with

(15) Tuleen, D. L.; Bennett, R. H. J. HeterocycL Chem. 1969,6, 115.

(E)-Thiacycloalk-4-enes

ice/20% sulfuric acid aind extracted with pentane. The residue after solvent evaporation was fractionally distilled to give 3 g (45%) of 2-vinylthiocane: bp 113 "C (16 mm); 'H NMR (60 MHz) 6 6.0-4.6 (m, 3 H, terminial vinyl group), 3.24 (m, 1 H, a-CH), 2.58 (unresolved m, 2 H, a-C:H2), 1.66 (wide, unresolved m, 10 H, 0-, y-, and 6-CHz's). Anal. Calcd for C9H16S: C, 69.16; H, 10.32. Found: C, 68.7; H, 10.45.

Thiocane was prepared by diimide reduction of thiacyclo- oct-4-ene (85:15 mixtuire of Z / E isomers).7c Oxygen gas was bubbled (0.2 L/min) through a solution of the olefin (3.84 g, 30 mmol), hydrazine hydrate (75 g, 1.5 mol), and 3 mL of 0.2 M aqueous CuS04 in 215 mL of ethanol maintained at 20 "C by external cooling. After 5 h no unreacted starting material re- mained (GLC, column A). Water (50 mL) was added and the mixture, made acidic with 15% HCl, was extracted with pentane. The extracts, washed with H,O and dried with CaS04, gave, after solvent removal and distillation under reduced pressure, 3 g (80%) of the title compound: bp 81-82 OC (14 mm) (lit.16 bp 70.5 OC (10 mm); 'H NMR 6 2.68 (m, 4 H, a-CH2), 1.65 (m, 10 H, 0-, y-, and 6-CHz). [Though comprising several steps, this synthesis of thiocane, which starts from thietane and allyl b r ~ m i d e , ' ~ , ~ ~ is superior to the direct cyclization method (overall 58%, against 34% in the final high-dilution cyclization of 1,7-dibromo- heptane)]

1-Ethyl-2-vinylthianium hexafluorophosphate (4a) was prepared by alkylation (Et30+BF4-) of 2-vinylthiane (1.28 g, 10 mmol) followed by metathesis with aqueous NH4PF6. Extraction with CH2C12 gave, after evaporation of the solvent, 2.7 g (90%) of a viscous uncrystalliicable material. The 'H NMR spectrum (D20) indicates one isomer (probably the trans)ls predominates (-1O:l): 6 5.75 (m, 3 H, olefinic protons), 4.05 (m, 1 H, a-CH), 3.5 (m, 4 H, a-CHis), 2.1 (large m, 6 H, 0- and y-CHis), 1.56 (t, 3 H, CH,). The presence of the minor isomer is indicated by a low-intensity triplet at 6 1.32. Anal. Calcd for CSH17SPF6: C, 35.76; H, 5.67. Found C, 35.63; H, 5.72. 1-Ethyl-2-vinylthiepanium hexafluorophosphate (4b) was

obtained (83%) as a viscous material from 2-vinylthiepane as described for the corresponding thiane derivative. The 'H NMR spectrum (60 MHz, D20) shows a large predominance of one isomer (probably the trms): 6 5.6 (m, 3 H, olefinic protons), 4.1 (m, 1 H, a-CH), 3.3 (large m, 4 H, a-CHis), 2.0 (large m, 8 H, 0- and yCHz's), 1.44 (t, 3 H, CH3). The presence of a minor isomer (5-10%) is revealed by a low-intensity triplet at 6 1.38. Anal. Calcd for Cl@,sSPF6: C, 37.97; H, 6.05. Found: C, 38.11; H, 6.10.

1-Ethyl-2-vinylthiooanium hexafluorophosphate (4c) was obtained (85%) as a viscous material from 2-vinylthiocane as described for the lower homologues. The presence of two geo- metrical isomers in -6:l ratio is apparent from both the 'H and 13C NMR spectra: 'H NMR (100 MHz, D20) 6 5.72 (m, 3 H, olefinic protons), 4.24 (m, 1 H, a-CH), 3.4 (unresolved m, 4 H, a-CHz), 2.0 (large unresolved m, 10 H, 0-, y-, and 6-CHz), 1.48 (t, 3 H, CH3). The minor isomer's CH3 triplet shows up at 6 1.48. The 13C NMR (CDZClz) is characterized by two low-field reso- nances of the major isomer at 6 130.8 (d, CH=) and 124.6 (t, =CH2) while the corresponding resonances of the minor isomer occur at 6 127.5 and 125.9. This pattern conf i i s the major isomer is of the trans configuration.s The other resonances are (in parentheses the minor isomer) as follows: Cz, 59.8 (55.3); C8, 39.4 (35.7); CH,CH3, 36.8 (35.6); C3, 29.7 (28.9); C5 and C6f25.6 and 25.1, interchangeable (25.7 and 24.6 interchangeable); C3 and C7, 23.8 and 22.8, interchangeable (23.7 and 23.8, interchangeable); CH3, 8.9 (9.1). Anal. Calcd for ClIHzlSPF6: C, 40.00; H, 6.41. Found: C, 39.92; H, 6.50. (E)-2-Methylthiacyclonon-4-ene (la) was obtained by ring

expansion of 4a under the conditions described for the synthesis of thiacyclonon-4-ene (t-IBuOK in THF/t-BuOH, 101, at -40 O C ) ?

J. Org. Chem., Vol. 45, No. 18, 1980 3617

(16) Muller, A,; Funder-Fritzche, E.; Konar, W.; Rintersbacher-Wla- sak, E. Monatsh. Chem. 1953,84, 1206.

(17) Esclamadon, C. Gorman Patent 1925 697, Nov 27, 1969; Chem. Abst. 1970, 72, 42785.

(18) In thiane alkylation the product of equatorial attack normally predominates (80-909i ).18

(19) Barbarella, G.; Deinbech, P.; Garbed, A.; Fava, A. Tetrahedron 1976,32,1045. Eliel, E. L.; Willer, R. L. J. Am. Chem. Soc. 1977,99, 1936. (20) Cer6, V.; Paolucci, C., unpublished.

4a (10 mmol, 3.0 g) gave 1.1 g (70.5%) of crude sulfide containing (GLC) two products in a 251 ratio, unchanged after distillation, bp 95 OC (7 mm). The 13C NMR spectrum at 0 OC displays three sets of signals (ratio 17.5:7.5:1). The two major sets (see Table I for shifts) coalesce on warming, indicating that they correspond to the conformational isomers of the trans olefin, while the minor set, of which only seven lines are visible, remains unaffected [6 132.3 (CJ, 127.1 (C,), 39.8 (Cz), 35.1 (CJ, 32.9, 27.6, and 26.41. This minor product is probably the 2 olefin 5. The room-tem- perature 'H NMR spectrum (100 MHz) has 6 6.0-5.1 (m, 2 H, olefinic Hs), 3.03 (m, 1 H, a-CH), 1.5 and 2.7 (overlapping large and ill-resolved multiplets, indicating slow exchange between unequivalent sites, 10 H overall, a-, (I-, y-, and 6-CHis), 1.32 (d, 3 H, CH3). Anal. Calcd for C9H16S: C, 69.16; H, 10.32. Found: C, 69.32; H, 10.35. (E)-2-Methylthiacyclodec-4-ene (2). Ring expansion of 4b

(1.17 g) under the condition^'^ gave 0.45 g (80%) of a sulfide fraction containing (GLC and '% NMR) four products, 1.7:6.1:221 (order of increasing retention time), which were separated by preparative GLC (column A, 130 "C).

The material with the shortest retention time is 2-vinylthiepane, arising from a @-elimination of ethylene. The material eluted second, m / e 170, was identified from its 'H and 13C NMR spectra as a ring-opened sulfide, ethyl octa-5,7-dien-l-yl sulfide (7), arising from a 0-elimination involving one of the protons at C3: 'H NMR d 6.5-5.5 (m, 3 H, CH=CHCH=), 5.0 (m, 2 H, =CH&, 2.54 (q,7.5 Hz, superimposed to a m, 4 H overall, CH,SCH.J, 2.11 (m, 2 H, CHzCH=), 1.55 (m, 4 H, SCH2CH2CH2), 1.24 (t, 3 H, CH,); '% NMR 6 137.3 (C7), 134.8 (c&, 131.4 (C5), 114.9 (CJ, 32.1 (e1), 31.5 (C2), 29.1 and 28.9 (C3 and C4 interchangeable), 26.0

Consistent with previous e~idence,~" the minor and major products, both m / e 170, were assigned the (Z)-(6) and (E)-2- methylthiacyclodec-4-ene (2) structure. The assignment is in accord with the 13C spectra, showing the resonances of the major isomer to be at low field relative to those of the minor isomer, as expected for a trans-cis pair '% NMR (CDzC1,; minor isomer in parentheses) 6 130.4 and 128.4 (130.4 and 128.4), C5 and C4, interchangeable; 44.2 (40.3), C,; 42.4 (35.0), C3; 31.9, 31.6, 28.3, 26.1, 24.0, and 23.6 (28.9, 26.5, 26.0, 24.4, 22.0, and 20.8), unas- signed. (For the low-temperature spectrum of 2, see Table I.) For either isomer the olefinic proton NMR absorption (100 MHz) is narrow and is unresolved by decoupling experiments.

Eisomers: NMR 6 5.56 (m, 2 H, olefinic H), 2.74 (m, 1 H), 2.54 (m, 2 H, a-CH,), 2.4 (m, 1 H), 2.1 (large m, 3 H), 1.6 (m, 6 H), 1.21 (d, 3 H, CH3). Anal. Calcd for CloH18S: C, 70.52; H, 10.65. Found: C, 70.24; H, 10.75.

Zisomer: NMR 6 5.54 (m, 2 H, olefinic H), 2.91 (m, 2 H), 2.4 (m, 2 H), 2.1 (m, 1 H), 1.6 (m, 6 H), 1.42 (d, 3 H, CH,). Anal. Calcd for C1JIl8S: C, 70.52; H, 10.65. Found C, 70.77; H, 10.61.

Attempted Ring Expansion of 1-Ethyl-2-vinylthiocanium Hexafluorophosphate (4c). The title salt (0.74 g, 2.24 mmol), subjected to the usual ring-expansion conditions, gives 0.34 g of a sulfide fraction whose GLC (column A, 150 O C ) shows two major peaks, 80% and 9%, respectively, besides five additional minor peaks. The materials giving the two more intense peaks were separated by preparative GLC (column A, 160 "C) and the major one was a -1:l mixture of 6-(E)- and 6-(Z)-nona-6,8-dien-l-y1 ethyl sulfide (8): 'H NMR 6 6.8-4.9 (m, 5 H, olefinic H's), 2.52 (q superimposed to a m, 4 H overall, CH2SCH2), 2.13 (m, 2 H, C5H2), 1.44 (m, 6 H, 0-, y-, and 6-CH2), 1.23 (t, 3 H, CH3). That the material was a mixture of isomers is evident from the '% NMR showing eight olefinic carbon resonances (six doublets at 6 137.3, 135.0, 132.5, 132.3, 131.2, and 129.5 and two triplets at 116.8 and 114.7), whose intensities are too close to permit assignment to one or the other isomer. The aliphatic region has five double- intensity resonances at 6 31.6, 29.6, 28.5, 26.0 (SCH2), and 14.8 (CH,), in addition to four resonances at 6 32.5,29.3,28.9, and 27.6.

The second more abundant product is ethyl 1-vinylhept-6- en-1-yl sulfide (9) from its 'H and 13C NMR: 'H NMR 6 6.03-5.43 (m, 2 H overall, 2 CH=), 5.12-4.85 (m, 4 H, 2 ==CHz), 3.17 (m, 1 H, SCH), 2.45 (4, 2 H, SCH,), 2.05 (m, 2 H, C5H2), 1.46 (m, 6 H, 0-, y-, and 6-CH2), 1.21 (t, 3 H, CH,). The 13C NMR spectrum has four olefinic [6 139.6 and 138.8 (2 =CH), 114.7 and 114.4 (2 =CH2)] and seven saturated carbon resonances 6 48.2 (CHS), 34.1, 33.6, 28.7, 26.8, 24.3 (S-CH2), and 14.6 (CH3).

(Cy), 14.8 (CH3).

3618 J. Org. Chem. 1980,45, 3618-3620

(E)-2-(Carbomethoxy)thiacycloundec-4-ene (3). A mixture of 2-vinylthiocane (0.78 g, 5 mmol), methyl diazoacetate (1.0 g, 10 mmol), and dry CuS04 (0.1 g) in 3 mL of benzene was heated at 40-45 "C under nitrogen. Gas evolution started immediately and continued without further external warming for about 5 min. The mixture was refluxed for 5 min, cooled, and filtered. Solvent evaporation left a residue (1.42 g) whose GLC (column B, 150 "C) showed one major peak (-65%) along with eight additional peaks of shorter retention time. The major product was separated by preparative GLC (150 "C): 'H NMR 6 5.9-5.4 (m, 2 H, olefinic

2.9-2.2 (m, 4 H), 2.1 (m, 2 H), 1.5 (m, 8 H). By irradiation a t 6 2.6, the high-field part of an olefinic AB quartet can be decoupled, J = 15.0 Hz, confirming the E double bond configuration. (For the 13C NMR spectrum, see Table I.) Anal. Calcd for ClzH&3O2: C, 63.11; H, 8.82. Found: C, 62.92; H, 9-01. (E)-2-(Carbomethoxy)thiacyclonon-4-ene (lb) was prepared

(50%) as described for the eleven-membered analogue, except that separation from the side products was performed via the HgC12 adduct. The sulfide was regenerated by aqueous KI treatment.7c The I3C spectrum at room temperature shows slow exchange between two conformers (Tables I and 11). Coalescence is observed on warming, and a t 80 OC a sharp ten-signal spectrum

H's), 3.76 (9, 3 H, CH3), 3.08 (q, J 11.0 and 3.5 Hz, 1 H, SCH),

is obtained (C2C14): 6 172.6 (CO), 136.5 (C5), 125.0 (C4), 51.9 and 51.6 (Cz and OCH3, interchangeable), 37.3 (C3), 35.9, 25.8, 25.0 (unassigned). The room temperature 'H NMR spectrum is also indicative of two diastereoisomers: the olefinic H absorption occurs as 2 multiplets a t 6 6.1-5.5 and 5.4-5.0, 1.25 and 0.75 H, respectively. The latter is a neat ddd pattern (J = 15.0, 10.0, and 4.0 Hz), while the former is a ddd pattern ( J = 15.0,9.5, and 4.0 Hz) centered a t 6 5.87 superimposed to an unresolved multiplet at 6 5.7. The behavior is consistent with the major isomer (-75%) giving raise to a two ddd pattern, with the minor isomer absorption occurring a t 6 5.7 for both olefinic protons. This behavior is consistent with previous observations of the corresponding 2- carbethoxy d e r i ~ a t i v e . ~ ~ Anal. Calcd for CI0Hl6O2S: C, 60.00; H, 8.06. Found: C, 59.63; H, 8.12.

Registry No. l a , 74263-06-2; l b (isomer l), 74263-07-3; l b (iso- mer 2), 74310-57-9; 2, 74263-08-4; 3, 74263-09-5; cis-la, 74263-11-9; trans-la, 74263-13-1; cis-4b, 74263-15-3; trans-lb, 74263-17-5; cis-lc, 74263-19-7; trans-lc, 74263-21-1; 5,74263-22-2; (276,74263-23-3; 7,

chlorothiocane, 74263-27-7; vinyl bromide, 593-60-2; 2-vinylthiocane, 74263-28-8; (E)-thiacyclooct-4-ene, 64945-41-1; (Z)-thiacyclooct-4- ene, 64945-38-6; thiocane, 6572-99-2; 2-vinylthiepane, 66120-30-7.

74263-24-4; (E)-& 74263-25-5; (2)-8, 74263-29-9; 9, 74263-26-6; 2-

Atropisomerism in o-Arylacetyl-N,N-dimethylbenzamides'

Paul R. Jones,* Gary R. Weisman,* Maurice J. Baillargeon,2a and Thomas A. GosinkZb Department of Chemistry, University of New Hampshire, Durham, New Hampshire 03824

Received October 29, 1979

A series of o-arylacetyl-N,N-dimethylbenzamides, 1-7, being studied as models for chain tautomers, differed markedly in their 'H NMR spectral properties, as a function of the Substituents R1-R4. In the two cases where substituents were placed ortho to the amide group, the benzylic protons were anisochronous at ambient temperatures. Reported dynamic 'H NMR results are consistent with concomitant C-N and aryl-CO torsional processes. The

carbonyl shifts are compared with those of model compounds.

In connection with a dynamic NMR study of ring-chain tautomerism, we have prepared a series of N,N-di- methylamides, 1-7, of o-arylacetylbenzoic acids from the corresponding enol lactones (eq 1). These, in turn, had

+ Me2NH

compd

1 2 3 4 5 6 7

I R4

1-7 R* R, R4

H H H H H Me

H c1

H NO* c1 c1 H H H H H H H H H

Rs H H H H o -Me p-c1 P-NO,

(1) Presented in part at the 178th National Meeting of the American Chemical Society; Washington, DC, 1979; Abstract No. ORGN 196.

(2) (a) University of New Hampshire Undergraduate Research Par- ticipant, Summer 1972; (b) National Science Foundation College Teacher Research Participant, 1971.

0022-3263/80/ 1945-3618$01.00/0

each been prepared by condensation of an arylacetic acid under aldol conditions3 with a phthalic anhydride; the exception was the enol lactone precursor of 3,4 which was obtained by aldol condensation of benzaldehyde with 6- nitr~phthalide.~ To our surprise, the benzylic protons in amides 2 and 4 were anisochronous, appearing as well- resolved AB quartets a t ambient temperature. All the other amides exhibited the expected singlet for the COC- HzAr group. Inasmuch as infrared spectra ruled out the nucleophilic6 ring tautomeric structure 8, we attribute the nonequivalence of the benzylic protons in 2 and 4 to atropisomerism,' the result of restricted rotation about the aryl-carbonyl bond of the amide functional group (vide infra).

I NMe2

8

Results of dynamic 'H NMR studies of 2, 4, and 5 are given in Table I. Data for high-temperature coalescence of both the benzylic and N-methyl resonances are shown for 2 and 4. Low-temperature dynamic behavior of the benzylic resonance of 5 is also reported. Calculation of

(3) Weiss, R. "Organic Syntheses"; Wiley: New York, 1943; Collect.

(4) Zimmer, H.; Barry, R. D. J. Org. Chem. 1962, 27, 3710-11. (5) Tasman, A. Recl. Trau. Chim. Pays-Bas 1972,46, 661. (6) Jones, P. R. Chem. Reu. 1963,63, 461-87. (7) Eliel, E. "Stereochemistry of Carbon Compounds"; McGraw-Hill:

Vol. 11, p 61.

New York, 1962; p 156.

0 1980 American Chemical Society